{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:00:49Z","timestamp":1790017249672,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Reproduction Devel"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pyroptosis, a proinflammatory form of programmed cell death mediated by the NLRP3 inflammasome, has recently been implicated in Sertoli cell inflammatory injury. Crocin, a water\u2010soluble carotenoid glycoside derived from\n                    <jats:italic>Crocus sativus<\/jats:italic>\n                    L. and\n                    <jats:italic>Gardenia jasminoides<\/jats:italic>\n                    Ellis, exhibits anti\u2010inflammatory, antioxidant, and anti\u2010apoptotic properties, yet its role in Sertoli cell pyroptosis remains unclear. Here, we investigated the pharmacological effects and mechanisms of crocin in regulating TM4 Sertoli cell viability and pyroptosis. Network pharmacology based on oligoasthenospermia (OA)\u2010related candidate targets, together with molecular docking, identified HSP90AA1 as a candidate molecular target associated with crocin\u2010mediated regulation of Sertoli cell pyroptosis. MST analysis further provided target\u2010engagement evidence supporting a direct interaction between crocin and HSP90AA1. In TM4 Sertoli cells, crocin improved cell viability, enhanced Ki\u201067 expression, and protected against lipopolysaccharide\/nigericin\u2010induced pyroptosis, as evidenced by reduced lactate dehydrogenase release, decreased PI\u2010positive cells, and downregulated expression of IL\u20101\u03b2, IL\u201018, NLRP3, Caspase\u20101, and GSDMD. Moreover, under HSP90AA1\u2010overexpressing conditions, crocin partially reduced pyroptosis\u2010related injury and inflammatory mediator expression, supporting the involvement of HSP90AA1 in crocin\u2010mediated regulation of Sertoli cell pyroptosis. Collectively, these findings indicate that crocin enhances Sertoli cell proliferation and mitigates inflammasome\u2010driven pyroptosis through an HSP90AA1\u2010associated mechanism. These findings should be interpreted as preliminary in vitro evidence for crocin\u2010mediated regulation of Sertoli cell proliferation and pyroptosis, and further validation in animal models and clinical samples is required.\n                  <\/jats:p>","DOI":"10.1002\/mrd.70135","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T12:27:44Z","timestamp":1783600064000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Crocin Targets HSP90 to Suppress NLRP3\/Caspase\u20101\u2013Mediated Sertoli Cell Pyroptosis"],"prefix":"10.1002","volume":"93","author":[{"given":"Yang","family":"Sun","sequence":"first","affiliation":[{"name":"The First School of Clinical Medicine Nanjing University of Chinese Medicine Nanjing Jiangsu China"},{"name":"Affiliated Hospital of Nanjing University of Chinese Medicine Jiangsu Province Hospital of Chinese Medicine Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haipeng","family":"Pei","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine Nanjing University of Chinese Medicine Nanjing Jiangsu China"},{"name":"Affiliated Hospital of Nanjing University of Chinese Medicine Jiangsu Province Hospital of Chinese Medicine Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0591-2917","authenticated-orcid":false,"given":"Xing","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine Nanjing University of Chinese Medicine Nanjing Jiangsu China"},{"name":"Affiliated Hospital of Nanjing University of Chinese Medicine Jiangsu Province Hospital of Chinese Medicine Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Jing","sequence":"additional","affiliation":[{"name":"The First School of Clinical 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Hospital of Chinese Medicine Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaying","family":"Qian","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine Nanjing University of Chinese Medicine Nanjing Jiangsu China"},{"name":"Affiliated Hospital of Nanjing University of Chinese Medicine Jiangsu Province Hospital of Chinese Medicine Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjuan","family":"Chang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Nanjing University of Chinese Medicine Jiangsu Province Hospital of Chinese Medicine Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Geng","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine Nanjing University of Chinese Medicine Nanjing Jiangsu China"},{"name":"Affiliated Hospital of Nanjing University of Chinese 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J. Tu L. Ji et al. 2025. \u201cIcariin Inhibition of NLRP3\u2010Mediated Leydig Cell Pyroptosis and Insulin Resistance Ameliorates Spermatogenesis Disorders in Obese Mice.\u201dInternational Immunopharmacology151: 114280.https:\/\/doi.org\/10.1016\/j.intimp.2025.114280.","DOI":"10.1016\/j.intimp.2025.114280"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01359-y"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.29826"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.01.042"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2023.113886"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-024-00796-x"}],"container-title":["Molecular Reproduction and Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mrd.70135","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mrd.70135","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mrd.70135","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:08:25Z","timestamp":1790014105000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mrd.70135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":40,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/mrd.70135"],"URL":"https:\/\/doi.org\/10.1002\/mrd.70135","archive":["Portico"],"relation":{},"ISSN":["1040-452X","1098-2795"],"issn-type":[{"value":"1040-452X","type":"print"},{"value":"1098-2795","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2025-09-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70135"}}